Povetacicept for Autoimmune Kidney Diseases

(RUBY-3 Trial)

Recruiting at 34 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Alpine Immune Sciences, Inc.

Must be taking: ACEis/ARBs

Must not be taking: B cell depleting

Disqualifiers: Other renal disease, eGFR <30, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to evaluate multiple dose levels of povetacicept in adults with immunoglobulin A (IgA) nephropathy, membranous nephropathy, lupus-related kidney disease (lupus nephritis). or anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis to determine if povetacicept is safe and potentially beneficial in treating these diseases. During the study treatment period, participants will receive povetacicept approximately every 4 weeks for 6 months, with the possibility of participating in a 6-month treatment extension period and an optional 52 week treatment extension period .

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, for some conditions, you should not be on background immunosuppression therapies, except for certain cases like lupus nephritis where stable immunosuppression is required. It's best to discuss your specific medications with the trial team.

How is the drug Povetacicept different from other treatments for autoimmune kidney diseases?

Povetacicept is unique because it targets specific immune system pathways involved in autoimmune kidney diseases, potentially offering a novel approach compared to existing treatments that may not specifically address these pathways. ^{1 2 3 4 5}

Research Team

Jiahua Li, M.D.

Principal Investigator

Alpine Immune Sciences, Inc.

Eligibility Criteria

Adults with certain autoimmune kidney diseases like IgA nephropathy, membranous nephropathy, or lupus-related kidney disease can join. They must have a confirmed diagnosis through biopsy and meet specific criteria including protein levels in urine and antibody presence. Stable immunosuppression treatment is required for some conditions before starting the trial.

Inclusion Criteria

I was diagnosed with IgA nephropathy less than 10 years ago and have a UPCR of 0.5 or higher without any immunosuppression treatments.

Indication-specific criteria:

I have a kidney condition confirmed by a biopsy and specific antibodies, with high protein levels in my urine or not enough decrease in protein despite treatment.

Exclusion Criteria

I have been diagnosed with another kidney disease.

My kidney function is severely reduced.

I have not had a serious infection recently or ongoing.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive povetacicept approximately every 4 weeks for 6 months

24 weeks

6 visits (in-person)

Treatment Extension

Participants may continue treatment for an additional 6 months

24 weeks

Optional Treatment Extension

Participants may opt into an additional 52-week treatment extension

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Povetacicept (Immunomodulator)

Trial Overview The study tests povetacicept (ALPN-303) to see if it's safe and effective for treating autoimmune kidney diseases. Participants will receive doses every four weeks for six months, with an option to continue for another six months.

Participant Groups

Group I: Povetacicept Experimental Treatment 1 Intervention

Participants will receive Povetacicept for 24 weeks with the possibility of participating in treatment extensions through 104 weeks of treatment.

Who Is Running the Clinical Trial?

Alpine Immune Sciences, Inc.

Lead Sponsor

Trials

9

Recruited

770+

Findings from Research

The study found that injecting an antibody against dipeptidyl peptidase IV (DPPIV) in rats led to significant proteinuria, indicating that this antibody directly affects glomerular cells and disrupts their function.

The results suggest that the proteinuria is caused by the binding of the anti-DPPIV antibody to the DPPIV present on glomerular cell membranes, rather than serum DPPIV, highlighting a specific mechanism of action in the development of kidney-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proteinuria induced by anti-dipeptidyl peptidase IV (gp108); role of circulating and glomerular antigen. Natori, Y., Shindo, N., Natori, Y.[2019]

DPP-4 inhibitors, like alogliptin, can reduce inflammation in the kidneys by decreasing the number of inflammatory macrophages, which may help in treating kidney diseases even in non-diabetic conditions.

The study suggests that the anti-inflammatory effects of DPP-4 inhibitors may work through glucagon-like peptide-1 signaling, indicating a potential new mechanism for their use in kidney disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-inflammatory role of DPP-4 inhibitors in a nondiabetic model of glomerular injury. Higashijima, Y., Tanaka, T., Yamaguchi, J., et al.[2018]

In a mouse model of chronic graft-versus-host disease, a significant reduction in Dipeptidyl peptidase IV (DPP IV) enzyme activity was observed as early as 4 weeks post-induction, indicating a potential early biomarker for kidney damage.

The impairment of DPP IV function may contribute to structural and functional kidney lesions, such as albuminuria and podocyte effacement, suggesting that targeting DPP IV could be a therapeutic strategy in lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redistribution of glomerular dipeptidyl peptidase type IV in experimental lupus nephritis. Demonstration of decreased enzyme activity at the ultrastructural level. van Leer, EH., Bruijn, JA., Prins, FA., et al.[2010]

A new monoclonal antibody against Dipeptidyl peptidase IV (DPPIV) effectively suppressed proteinuria and mesangial proliferation in Wistar rats with immune complex-mediated glomerulonephritis, indicating DPPIV's potential role in this condition.

The study suggests that DPPIV regulates the complement cascade, and inhibiting it could be a promising strategy for preventing tissue injury related to complement activation, as shown by the inactivation of the complement cascade in treated rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involvement of dipeptidyl peptidase IV in immune complex-mediated glomerulonephritis. Shinosaki, T., Kobayashi, T., Kimura, K., et al.[2023]

In a study of 159 patients with type 2 diabetic nephropathy, the combination of dipeptidyl peptidase-4 inhibitors (DPP4i) and angiotensin receptor blockers (ARBs) resulted in a slower decline in kidney function (eGFR) compared to ARBs alone after 12 months.

The combined treatment also led to a greater reduction in proteinuria over 24 months, indicating enhanced renoprotection that was independent of changes in blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renoprotection Provided by Dipeptidyl Peptidase-4 Inhibitors in Combination with Angiotensin Receptor Blockers in Patients with Type 2 Diabetic Nephropathy. Qiu, DD., Liu, J., Shi, JS., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Proteinuria induced by anti-dipeptidyl peptidase IV (gp108); role of circulating and glomerular antigen. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Anti-inflammatory role of DPP-4 inhibitors in a nondiabetic model of glomerular injury. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Redistribution of glomerular dipeptidyl peptidase type IV in experimental lupus nephritis. Demonstration of decreased enzyme activity at the ultrastructural level. [2010]

4. United States pubmed.ncbi.nlm.nih.gov

Involvement of dipeptidyl peptidase IV in immune complex-mediated glomerulonephritis. [2023]

5. China pubmed.ncbi.nlm.nih.gov

Renoprotection Provided by Dipeptidyl Peptidase-4 Inhibitors in Combination with Angiotensin Receptor Blockers in Patients with Type 2 Diabetic Nephropathy. [2022]